The important physiological role of copper in vertebrates was first demonstrated in 1928. Since that time, copper was found to be a key component of several enzymes. Most of these copper-containing enzymes are known to catalyze physiologically important reactions. Dietary deficiency of copper in vertebrates results in several pathological disorders.
One early manifestation of copper deficiency is spontaneous fracture of bones in sheep and cattle that graze in copper-deficient pastures. Experimentally induced copper deficiency resulted in bone abnormalities in rabbits, pigs, chickens and dogs. The bone defect appears to reside in the organic matrix and not in the mineral make-up of the bone.
Copper deficiency results in the failure of pigmentation of hair and wool in numerous species including black-wooled correlated with copper supplementation. Feathers of turkey poults fed copper-deficient diets also show lack of pigmentation.
Copper deficiency can cause cardiac lesion in cattle which may even result in sudden death. Further, chicks and pigs fed copper-deficient diets may die suddenly from massive internal hemorrhage due to structural defects in major arteries.
Subnormal levels of copper in the forage has resulted in neonatal ataxia or swayback in lambs. Copper-deficient pigs do not absorb iron at a normal rate. It appears that copper is also essential for the release of iron from the intestinal mucosa and iron storage tissues. In general, copper deficiencies cause anemia in all the species that have been studied so far.
Only a fraction of the copper ingested in diet is ultimately utilized in the formation of copper-proteins. The form of the copper ingested influences the degree of its utilization as measured by ceruloplasmin (copper-protein enzyme) activity. The presence of some amino acids have been known to cause an increase in the absorption and utilization of copper. (Kirchgessner and Girassmann, Z. Tierphysiol. Tierenahrung Futtermittelk. 26:3 (1970; Girassmann et al., Z. Tierphsiol. Tierernahrung Futtermittelk. 28:28 (1971); Schwarz et al., ibid. 31:98 (1973).)
It can, therefore, be seen that proper dietary balance of highly bioavailable copper is important for animals, including swine and poultry. In recent times, it has been reported, particularly for swine and poultry, that they may have copper deficiencies because of the nature of their food rations. Put another way, it has been found that from time to time, mycotoxins which are present in food rations, particularly corn, have a tendency to tie up the available copper in a form which makes it non-bioavailable. Thus, the net result is that the feed for the swine and the poultry containing mycotoxins may in some way bind the available copper in the food to make it non-bioavailable. The net result is that even though one feeds to the animals much higher levels of copper than the NRC (National Research Council) recommended daily allowances, the animal does not get anywhere near its adequate NRC requirement.
An additional problem is caused by feeding high levels of copper which are simply thereafter excreted without uptake. The copper in the excretement is returned to the soil, significantly raising the copper level. This may cause undesired environmental polluting problems.
It therefore can be seen that adequate dietary levels of highly bioavailable copper are necessary for development of livestock, including cattle, swine and poultry. Moreover, there is a need to present copper in a highly bioavailable form which assures that the animal will have a high level of uptake of the copper without excreting it to cause potential environmental pollution.
It is an especially preferred advantage to make the complexes of the present invention from essential amino acids. This allows not only for increased bioavailability of the copper, but also it allows the animal a proper nutritional amount of an essential amino acid necessary for proper growth. For copper, it is especially difficult to form solid form complexes of copper and alpha-amino acids. For example, if one attempts to form such a complex with methionine in accord with the general procedures outlined in U.S. Pat. No. 3,941,818 issued Mar. 2, 1976 and U.S. Pat. No. 4,021,569 issued May 3, 1977, the result is an oxidation-reduction reaction between the methionine and the copper, resulting in an unuseable reaction product. It has now been discovered that when copper complexes of alpha-amino acids having a terminal amine group are employed, the internal redox reaction does not occur.
It is therefore a primary objective of the present invention to provide a highly effective bioavailable form of copper in convenient water soluble salt form which is available for use as a feed additive in animal nutrition.
Another important objective of the present invention is the preparation of new, complex salts of copper in which the copper is in a form that can be readily absorbed after ingestion by livestock, particularly swine, poultry and cattle.
Yet another objective of the present invention is to provide complexed salts of copper which, because of the complexing of copper with certain alpha-amino acids containing a terminal amine moiety, are shelf stable.
An even further objective of the present invention is to provide a method of nutritional supplementation for animals to assure adequate dietary requirements of copper for growth and health.
An even further objective of the present invention is to provide certain complex salts of copper and certain alpha-amino acids containing a terminal amine moiety, such as lysine, which have coordination bonds formed between the copper ion and the alpha-amino group of the acid, in addition to an electrostatic attraction bond between the cation and the carboxyl ions.
An even more specific objective of the present invention is to prepare 1:1 ratio complexes wherein the ratio of copper to the alpha-amino acid is 1:1.
The method of accomplishing these as well as other objectives of the invention will become apparent from the detailed description of the invention which follows hereinafter.